| Unanswered questions |
| 1) What are the roles and mechanisms of alloimmune and autoimmune responses in BOS pathogenesis? |
| 2) Does antibody-mediated rejection play a role in BOS onset and progression? |
| 3) What is the significance of the appearance of de novo anti-HLA antibodies in BOS pathogenesis, and when and how should screening and treatment for anti-HLA antibodies be performed? |
| 4) Can specific biomarkers identify and reliably predict increased risk for the development of BOS, and can such biomarkers be used to detect the early (subclinical) onset of BOS? |
| 5) Can specific BOS phenotypes be identified that are useful for predicting prognosis and response to therapy? |
| 6) Which specific agent or combinations of post-transplant immunosuppressive agents are most likely to prevent BOS and improve allograft and patient survival? |
| 7) Does any early, specific therapy significantly alter the natural history of BOS? |
| 8) When lung retransplantation is performed for end-stage BOS, is the retransplanted lung at increased risk for the development of rejection and/or OB? |
| 9) Can patients who are more tolerant to their grafts and, therefore, require less intense immunosuppression be identified? |
| 10) Can induction of tolerance to self-antigens (e.g. collagen V) or strategies to augment regulatory T- or B-cells to promote and maintain tolerance diminish risk for BOS? |
| 11) Will the use of ex vivo lung perfusion (EVLP) techniques to condition the lung allograft diminish the risk of developing BOS? |
| 12) What is the optimal frequency for obtaining spirometry to assist in the early detection of evolving BOS? |
| Research needs |
| 1) Multi-centre clinical investigations are needed to identify and assess risk factors for BOS. |
| 2) Multi-centre clinical trials are needed to evaluate potential therapeutic interventions to treat BOS as well as strategies to prevent its onset. |
| 3) Additional studies of mechanisms and phenotypes (animal models and lung allograft recipients) are needed. |
| 4) Guidelines for optimal testing for abnormal GOR and the selection of patients (and procedure) for anti-reflux surgery to prevent or treat BOS. |
| 5) Identification of optimal approaches to allograft surveillance (e.g. the role of bronchoscopy with transbronchial biopsies in clinically stable lung transplant recipients, screening for de novo anti-HLA antibodies and the presence of humoral rejection). |
| 6) Improved animal and other laboratory models of OB to better understand its pathogenesis and identify key mediators of airway inflammation and fibrosis. |
BOS: bronchiolitis obliterans syndrome; HLA: human leukocyte antigen; OB: obliterative bronchiolitis; GOR: gastro-oesophageal reflux.